Safety and Pharmacokinetics of Clindamycin in Pediatric Subjects With BMI ≥ 85th Percentile

Phase 1

Completed

• Conditions: Bacterial Infections; Obesity
• Interventions: Drug: Clindamycin

• Registration Number: NCT01744730
• Lead Sponsor: Phillip Brian Smith

Brief Summary

The purpose of this study is to better understand how clindamycin works in children who fall in the 85th percentile or higher for body mass index (BMI - a ratio of weight to height). The results of the study will help better understand if children in higher BMI ranges process the medication differently and whether dosing should be adjusted in these children.

Detailed Description

This is a prospective, open-label pharmacokinetic and safety study of multiple doses of IV and oral clindamycin in overweight and obese children ages 2 to 17 years of age. The total study duration is expected to be approximately 24 months; each subject will participate in the study for up to 18 days (screening day; treatment days 1-14 \[may be as short as 2 days\] followed by an observation period of 3 days post discontinuation of clindamycin therapy or after day 17 (on day 18) of therapy in those who are treated with more than 14 days of clindamycin).

Study Timeline

• Study First Submitted: 2012-12-05
• Study First Submitted QC: 2012-12-05
• Study First Posted: 2012-12-07
• Study Start: 2013-06
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Results First Submitted: 2016-02-10
• Status Verified: 2016-10
• Results First Submitted QC: 2016-10-18
• Results First Posted: 2016-10-19
• Last Update Submitted: 2016-11-21
• Last Update Posted: 2016-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• 2 years - < 18 years of age at the time of first dose of study drug
• Suspected or confirmed infection OR receiving IV clindamycin per routine care
• Negative serum pregnancy test (if female and has reached menarche) within 24 hours of first dose of study drug and agreement to practice appropriate contraceptive measures, including abstinence, from the time of the initial pregnancy test through the last dose of study drug
• BMI ≥ 85th percentile for age and sex, based on Centers for Disease Control (CDC) recommendations
• Signed informed consent/Health Insurance Portability and Accountability Act (HIPAA) documents by the parent/legal guardian and assent (if applicable)

Exclusion Criteria

• The following apply only to those who are NOT already receiving clindamycin per routine care:

  1. History of hypersensitivity or allergic reaction to clindamycin or lincomycin
  2. History of C. difficile colitis with previous administration of clindamycin
  3. Aspartate aminotransferase (AST) > 120 units/L
  4. Alanine aminotransferase (ALT) > 210 units/L
  5. Total bilirubin > 3 mg/dL
  6. Serum creatinine > 2 mg/dL
  7. Receiving a neuromuscular blocker as part of their therapy

• Previous participation in the study

• Subject is on prohibited medication or herbal product (see Appendix II)

• Subject is receiving extracorporeal life support (ECLS)

• Subject is post-cardiac bypass (within 24 hours)

• Subject on inotropes/pressors

• Any other condition or chronic illness that, in the opinion of the principal investigator, makes participation unadvised or unsafe

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Clindamycin IV-ages 12 to 17 (BMI Greater Than 95th)	Clindamycin	Clindamycin IV: Children ages 12 to 17 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.
Clindamycin IV-ages 2 to 11 Years Old (BMI 85-95th Percentile)	Clindamycin	Clindamycin IV: Children ages 2 to 11 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.
Clindamycin IV-ages 2 to 11 Years Old (BMI Greater Than 95th)	Clindamycin	Clindamycin IV: Children ages 2 to 11 years old with BMI greater than 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.
Clinidamycin IV-ages 12 to 17 (BMI 85-95th Percentile)	Clindamycin	Clindamycin IV: Children ages 12 to 17 years old with BMI 85th to 95th percentile. Their schedule of IV Clindamycin administration included 30-40 mg/kg/day dosed every 6 or every 8 hours with a maximum daily dose of 2.7 grams/day. Dosing greater than 2.7g/day was allowed for children receiving clindamycin as part of clinical care.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) - Clearance (Cl) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.	After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).	In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese and non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.; PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for clearance by age cohort normalized to 70 kg of body weight are presented below.; Sampling schedule details for PTN_POPS and Staph Trio were comparable.
PK - Volume of Distribution (V) in Participants Who Received Multiple Doses of Intravenous (IV) Clindamycin.	After first study dose of IV Clindamycin through Day 14 (minimum of 3 samples; maximum of 6 samples).	In order to understand the impact of obesity on clindamycin PK, PK data were combined to build a PK model from 3 studies that included both obese \& non-obese children: 1) PTN_Clinda Obese study (clinicaltrials.gov/ct.gov identifier NCT01744730) n = 21; 2) PTN_POPS study (ct.gov identifier NCT01431326) n = 178; and 3) Staph Trio study (ct.gov identifier NCT01728363) n = 21. The data from the Staph-Trio study were only included for PK modeling and not intended to be compared in the analysis.; PK sampling schedule for PTN_Clinda Obese was: Pre-dose 0 (within 15 minutes prior to IV clindamycin dose), 0.5 (± 5 minutes) after dose was administered, 1-1.5 hours (hrs) after dose, 3-4 hrs after, 5-6 hrs after, and pre-next dose. Samples were collected on multiple days and averaged to arrive at a single value. Comparison of EBE for volume of distribution by age cohort normalized to 1kg of body weight are presented below.; Sampling schedule details for PTN_POPS \& Staph Trio were comparable.

Trial Locations

Locations (4)

Ann and Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Kansas, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Akron Children's Hospital; 🇺🇸 Akron, Ohio, United States